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Epithelial-mesenchymal plasticity in circulating tumor cells

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Abstract

Epithelial-to-Mesenchymal Transition (EMT) is a complex process that supports the migratory capacity of epithelial tumor cells and is thought to play a crucial role in promoting cancer metastasis. Despite the wealth of experimental data, the exact role of EMT in cancer patients remains more controversial. Over the past 10 years, sensitive technologies that allow the detection and molecular characterization of circulating tumor cells (CTCs) in the peripheral blood of tumor patients have been developed. These analyses help to shed new light into the importance of EMT for human tumor cell dissemination. CTCs with mesenchymal features can be attributed in some clinical studies (in particularly on breast cancer) to higher disease stages, presence of metastases, and even to therapy response and worse outcome. However, the published studies addressing the impact of mesenchymal-like CTCs show heterogeneity with regard to assay specificity, size of cancer and control groups, and endpoint parameters. In the present review, we present the key features of the biology of CTCs in relation to epithelial-to-mesenchy-mal plasticity, describe the current technologies for enrichment and detection of CTCs with high epithelial-mesenchymal plasticity, and discuss the clinical studies that have assessed the relevance of mesenchymal CTCs in carcinoma patients.

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Abbreviations

EpCAM:

Epithelial cell adhesion molecule

EMT:

Epithelial-to-mesenchymal transition

E:

Epithelial

M:

Mesenchymal

Ab:

Antibodies

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Acknowledgements

The authors receive support from CANCER-ID, an Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115749, resources of which are composed of financial contribution from the European Union’s Seventh Framework Program (FP7/2007–2013) and EFPIA companies’ in-kind contribution. This work was further supported by the FEDER plus the Region Languedoc-Roussillon (GEPETOS project) and the National Institute of Cancer (INCA; to C. Alix-Panabières), and the European Research Council Advanced Investigator grant no. 269081 DISSECT (to K. Pantel).

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Authors and Affiliations

  1. Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, 641, avenue du Doyen Gaston Giraud, 34093, Montpellier Cedex 5, France

    Catherine Alix-Panabières

  2. EA2415 – Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research (IURC), Montpellier University, Montpellier, France

    Catherine Alix-Panabières

  3. Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Sonja Mader & Klaus Pantel

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  1. Catherine Alix-Panabières
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  2. Sonja Mader
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  3. Klaus Pantel
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Correspondence to Catherine Alix-Panabières or Klaus Pantel.

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Alix-Panabières, C., Mader, S. & Pantel, K. Epithelial-mesenchymal plasticity in circulating tumor cells. J Mol Med 95, 133–142 (2017). https://doi.org/10.1007/s00109-016-1500-6

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